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Yale researchers have identified human intestinal microbes that metabolize more than 150 therapeutic drugs, highlighting the role bacteria play in determining how well individuals respond to drugs, the June 3 Nature daily reported.
Scientists from the lab's lead author Andrew Goodman of the Yale Institute of Microbial Sciences and the Department of Microbial Pathogenesis also identified the microbial genes responsible for many drug metabolizing activities.
"It is possible that we can use genes or species of bacteria to predict the ability of an individual's intestinal flora to metabolize a certain drug, "said Maria Zimmermann-Kogadeeva, a postdoctoral fellow at Goodman's lab and co-author study. "This work is a first step in identifying biomarkers that can help physicians prescribe the safest and most effective drugs for each patient."
In the past, it was thought that the metabolism of drugs was exclusively the responsibility of human organs such as the liver, whose main task is to transform chemical compounds into water-soluble molecules to promote their elimination from the body. This process is essential to determine the effectiveness and safety of clinical drugs: Medications must remain in the body long enough to have an effect, but not long enough to accumulate and become potentially toxic.
Drug metabolism studies generally do not evaluate the contribution of the microbiome. "However, anecdotal examples of microbiome metabolized drugs have emerged in recent decades," said Goodman.
To map the links between intestinal microbes and drugs, researchers investigated whether and how each of the 271 drugs is chemically modified by each of 76 different types of human gut bacteria. Nearly two-thirds of these drugs were metabolized by at least one of the bacterial samples tested. The researchers then constructed genetic libraries of selected intestinal bacteria metabolizing the drugs, which allowed them to systematically identify many genes responsible for the chemical transformation of drugs.
They found that the number of these genes varied considerably among the intestinal microbial communities of healthy human volunteers. In some cases, these differences explain why some intestinal microbiomes metabolize drugs quickly while others modify the same drugs slowly or not at all.
"We hope this study will provide a useful first step in understanding the contribution of the microbiome to drug metabolism, "said Michael Zimmermann, a postdoctoral researcher at Goodman Lab and co-lead author of the study. "We believe these approaches could shed light on how the gut microbiome also modulates our response to non-drug compounds, such as dietary nutrients and environmental agents."
The work was mainly supported by the National Institutes of Health.
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